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Profile Name IDH1 R132C
Gene Variant Detail

IDH1 R132C (gain of function)

Relevant Treatment Approaches IDH Inhibitor (Pan) IDH1 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
IDH1 R132C sarcoma sensitive Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, Lynparza (olaparib) treatment delayed tumor growth in cell line xenograft models of sarcoma harboring IDH1 R132C (PMID: 28148839). 28148839
IDH1 R132C fibrosarcoma sensitive Ceralasertib + Olaparib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Lynparza (olaparib) and Ceralasertib (AZD6738) resulted in a greater delay in tumor growth compared to Ceralasertib (AZD6738) alone in fibrosarcoma cell line xenograft models harboring IDH1 R132C (PMID: 34027408). 34027408
IDH1 R132C sarcoma decreased response IDH1 Inhibitor AGI-5198 + Talazoparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C fibrosarcoma predicted - sensitive IDH Inhibitor (Pan) AG-881 Preclinical - Cell line xenograft Actionable In a preclinical study, AG-881 treatment decreased tumor 2HG levels in a fibrosarcoma cell line xenograft model harboring IDH1 R132C (Mol Cancer Ther Jan 1 2018 (17) (1 Supp) B126). detail...
IDH1 R132C high grade glioma sensitive Talazoparib Preclinical - Patient cell culture Actionable In a preclinical study, patient-derived glioma cells harboring IDH1 R132C demonstrated increased sensitivity to Talazoparib (BMN-673)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C Advanced Solid Tumor predicted - sensitive IDH1 Inhibitor DS-1001b Preclinical - Cell culture Actionable In a preclinical study, DS-1001b inhibited IDH1 R132C enzymatic activity in an in vitro assay, and inhibited production of the oncometabolite 2-hydroxyglutarate (2-HG) in transformed human cells expressing IDH1 R132C in culture (PMID: 31727689). 31727689
IDH1 R132C sarcoma decreased response IDH1 Inhibitor AGI-5198 + Olaparib Preclinical - Cell culture Actionable In a preclinical study, AGI-5198 reverted the sensitivity of sarcoma cells harboring IDH1 R132C to Lynparza (olaparib)-induced growth inhibition in culture (PMID: 28148839). 28148839
IDH1 R132C intrahepatic cholangiocarcinoma sensitive Saracatinib Preclinical Actionable In a preclinical study, intrahepatic cholangiocarcinoma cells harboring IDH1 R132C demonstrated increased sensitivity to Saracatinib (AZD0530) induced growth inhibition compared to IDH1 wild-type cells in culture (PMID: 27231123). 27231123
IDH1 R132C chondrosarcoma predicted - sensitive Olaparib Case Reports/Case Series Actionable In a Phase II trial (OLAPCO), Lynparza (olaparib) treatment resulted in a partial response with 59% tumor reduction lasting 14 months in one patient and stable disease lasting 7.5 months in one patient out of four patients with chondrosarcoma harboring IDH1 R132C (PMID: 34994649, NCT02576444). 34994649
IDH1 R132C acute myeloid leukemia sensitive IDH1 Inhibitor Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 21.6% (27/125), CR with partial hematological recovery (CRh) in 8.8% (11/125), and overall response (OR) in 41.6% (52/125) of patients with relapsed or refractory acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test (PMID: 29860938; NCT02074839). detail... detail... detail... 29860938
IDH1 R132C acute myeloid leukemia sensitive IDH1 Inhibitor Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase I trial that supported FDA approval, Tibsovo (ivosidenib) treatment resulted in complete remission (CR) in 28.6% (8/28), CR with partial hematological recovery (CRh) in 14.3% (4/28) of patients age 75 or older with untreated acute myeloid leukemia harboring a susceptible IDH1 mutation (R132C/G/H/L/S) as detected by an FDA-approved test, with a median treatment duration of 4.3 months (PMID: 29860938; NCT02074839). detail... 29860938 detail...
IDH1 R132C chondrosarcoma predicted - sensitive IDH1 Inhibitor Ivosidenib Case Reports/Case Series Actionable In a Phase I trial, Tibsovo (ivosidenib) treatment was tolerated, substantially decreased plasma 2-HG levels, and resulted in a median progression-free survival of 5.6 months and stable disease in 52% (11/21) of patients with chondrosarcoma harboring IDH1 mutations, including IDH1 R132C (n=13) (PMID: 32208957; NCT02073994). 32208957
IDH1 R132C acute myeloid leukemia sensitive IDH1 Inhibitor Azacitidine + Ivosidenib Phase Ib/II Actionable In a Phase Ib trial, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination treatment demonstrated a favorable safety profile and resulted in an objective response rate (ORR) of 78.3% (18/23, 14 complete remission) and a 12-month overall survival probability of 82% in patients with newly diagnosed acute myeloid leukemia harboring IDH1 R132C (n=14), R132H (n=4), or R132L (n=3) mutations (PMID: 33119479; NCT02677922). 33119479
IDH1 R132C acute myeloid leukemia sensitive IDH1 Inhibitor Azacitidine + Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase III trial (AGILE) that supported FDA approval, Tibsovo (ivosidenib) and Vidaza (azacitidine) combination therapy significantly improved event-free survival (HR 0.33, p=0.002) and median overall survival (24.0 vs 7.9 mo, HR 0.44, p=0.001) compared to Vidaza (azacitidine) plus placebo in patients with newly diagnosed acute myeloid leukemia harboring IDH1 mutations including R132C/H/G/L/S (PMID: 35443108; NCT03173248). 35443108 detail... detail...
IDH1 R132C intrahepatic cholangiocarcinoma sensitive Dasatinib Preclinical Actionable In a preclinical study, Sprycel (dasatinib) inhibited growth of intrahepatic cholangiocarcinoma cells harboring IDH1 R132C in culture, and suppressed tumor growth in PDX models (PMID: 27231123). 27231123
IDH1 R132C high grade glioma sensitive IDH1 Inhibitor AGI-5198 Preclinical Actionable In a preclinical study, AGI-5198 inhibited growth and promoted differentiation in glioma cells expressing IDH1 R132C (PMID: 23558169). 23558169
IDH1 R132C cholangiocarcinoma predicted - sensitive IDH1 Inhibitor Ivosidenib FDA approved - On Companion Diagnostic Actionable In a Phase III (ClarIDHy) trial that supported FDA approval, Tibsovo (ivosidenib) treatment significantly improved median progression-free survival (2.7 vs 1.4 mo, HR=0.37, p<0.001) and prolonged median overall survival (10.8 vs 9.7 mo, HR=0.69, p=0.06) compared to placebo in patients with advanced cholangiocarcinoma harboring IDH1 mutations including R132C/H/L/G/S, resulted in favorable objective response rate (2%, 3/124 vs 0%, 0/61) and stable disease rate (51% vs 28%) (PMID: 32416072; NCT02989857). detail... detail... 32416072
IDH1 R132C leukemia sensitive TETi76 Preclinical - Cell culture Actionable In a preclinical study, TETi76 treatment decreased viability of a leukemia cell line expressing IDH1 R132C in culture (PMID: 33681816). 33681816
IDH1 R132C acute myeloid leukemia sensitive IDH1 Inhibitor BAY1436032 Preclinical - Pdx & cell culture Actionable In a preclinical study, BAY1436032 decreased R-2HG levels and inhibited growth of primary acute myeloid leukemia (AML) cells harboring IDH1 R132C in culture, and decreased blast number and increased survival of two AML patient-derived xenograft (PDX) models, one which harbored additional alterations in FLT3, NPM1, and NRAS and one which harbored a KMT2A (MLL) alteration (PMID: 28232670). 28232670
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04164901 Phase III AG-881 Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO) Active, not recruiting USA | ITA | FRA | ESP | DEU | CAN 4
NCT03953898 Phase II Olaparib Using the Anticancer Drug Olaparib to Treat Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome With an Isocitrate Dehydrogenase (IDH) Mutation Recruiting USA 0
NCT04088188 Phase I Cisplatin + Gemcitabine + Pemigatinib Cisplatin + Gemcitabine + Ivosidenib Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma Recruiting USA 0
NCT04056910 Phase II Ivosidenib + Nivolumab Ivosidenib (AG-120) With Nivolumab in IDH1 Mutant Tumors Recruiting USA 0